Although a substantial body of knowledge exists on the mutagenic effects of chemicals and radiation in prokaryotes and lower eukaryotes, little is known about the mechanism of mutagenesis in human diploid cells. Clearly, if microbial test systems are to be used to evaluate the carcinogenic and mutagenic potential of environmental chemicals, knowledge of how microbial systems relate to human cells is essential. We have, therefore, begun a large project to investigate the induced forward mutation frequency at a haploid locus (x-linked locus, HGPRT) and at a diploid locus (autosomal locus, APRT) in human diploid fibroblasts. In addition, the induced revertant mutant frequency (HGPRT in Lesch Nyan cells) in human fibroblasts in a variety of sibships will be investigated. Partial characterization of these mutations will be possible with the use of selected compounds (ICR-170; ICR-191; MNNG; NA-AAF). We will also do the dosimetry of induced mutation frequency using radiolabeled MNNG and NA-AAF.